Adjuvants are agents that enhance immune responses (e.g., see “Vaccine Design: The Subunit and Adjuvant Approach”, Pharmaceutical Biotechnology, Volume 6, Eds. Powell and Newman, Plenum Press, New York and London, 1995). Adjuvants can be used in strategies for eliciting specific immune responses through the administration of vaccines.
Lipopolysaccharide (LPS) is a unique glycolipid found in the outer leaflet of the outer membrane of Gram-negative bacteria and has been shown to be a potent stimulator of the immune system. Unfortunately, its use in adjuvants has been curtailed by its toxic effects. A non-toxic derivative of LPS, monophosphoryl lipid A (MPL), produced by removal of the core carbohydrate group and the phosphate from the reducing-end glucosamine, has been described by Ribi et al (1986, Immunology and Immunopharmacology of Bacterial Endotoxins, Plenum Publ. Corp., NY, pp. 407-419). A further detoxified version of MPL results from the removal of the acyl chain from the 3-position of the disaccharide backbone, and is called 3-O-deacylated monophosphoryl lipid A (3D-MPL). Other MPL derivatives are described in U.S. Pat. No. 7,491,707 and U.S. Patent Publication Nos. 2008/0131466 and 2009/0181078. Despite these developments there remains a need in the art for new adjuvants including alternative chemically defined derivatives of MPL.